DEVELOPMENT OF AN ARG-GLY-ASP-BASED WOUND-HEALING AGENT

THE SLOW HEALING OR LACK OF HEALING OF WOUNDS SUCH AS DECUBITUS ULCERS, SEVERE BURNS, AND DIABETIC ULCERS IS A SERIOUS MEDICAL PROBLEM, AFFECTING MILLIONS OF INDIVIDUALS AND CAUSING SEVERE PAIN OR DEATH IN MANY PATIENTS. A MAJOR FACTOR CONTRIBUTING TO THE POOR HEALING RESPONSE SEEN IN THESE PATIENTS IS THE DESTRUCTION OF SPECIFIC EXTRACELLULAR MATRIX PROTEINS. CELLS INTERACT WITH THESE MATRIX COMPONENTS THROUGH ARG-GLY-ASP SEQUENCES PRESENT IN SUCH MOLECULES AS FIBRONECTIN, VITRONECTIN, COLLAGEN, AND TENACIN. SUCH ATTACHMENT ALLOWS THE CELLS TO MOVE THROUGH THE MATRIX, AS IN FIBROBLAST MIGRATION INTO WOUNDS. BY PROVIDING A SYNTHETIC MATRIX, IT IS BELIEVED THE HEALING PROCESS CAN BE INFLUENCED IN WOUNDS OF THE TYPE MENTIONED ABOVE. THIS WORK IS DESIGNED TO DEVELOP A SYNTHETIC MATRIX COMPOSEDOF RGD-CONTAINING PEPTIDES COUPLED TO A BIODEGRADABLE POLYMER, THEREBY PROVIDING A METHOD OF STIMULATING CELL MIGRATION INTO THE WOUND IN A TIME EXPECTED TO BE SHORTER THAN IF THE CELLS WERE REQUIRED TO SYNTHESIZE THE MATRIX THEMSELVES. EACH OF THREE COMPONENTS (PEPTIDE, POLYMER, ANDCOUPLING CHEMISTRY) WILL BE ANALYZED TO ACHIEVE A COMPOUND THAT BEHAVES BEST IN IN VITRO ASSAYS DESIGNED FOR THIS PURPOSE. THE MATERIAL WILL THEN BE TESTED IN AN ACCEPTED ANIMAL WOUND-HEALING MODEL TO DETERMINE IF HEALING TIME AND INTEGRITY OF THE HEALING WOUND BED CAN BE AFFECTED.